Recent investigations with focus on regeneration of the periodontium have attempted to define the biological factors involved in formation of a new connective tissue attachment. Essential biological events involved in tissue regeneration are chemotaxis and proliferation. Extracellular matrix proteins have been shown to influence chemotaxis, cell proliferation and differentiation. The extracellular matrix proteins fibronectin and laminin and the polypeptide growth factors have been shown to stimulate a variety of biological processes. For example, laminin and fibronectin when bound to dentin surfaces act in a reciprocal manner to stimulate the directed migration and proliferation of gingival epithelial cells and of periodontal ligament cells respectively. We hypothesize that biochemical manipulation of dentin through selective use of matrix proteins and growth factors will provide a favorable substrate for regeneration of the peridontal ligament. Here we propose to fully characterize and develop an in vitro assay system that tests the capacity of various biological response modifiers applied on dentin to stimulate a chemotactic and proliferative response in various cell types of the periodontium. The assay system is divided into two assays. Assay I is concerned with the chemotactic activity of dentin bound test factors. Here cells must actively move through a Nuclepore filter towards a dentin bound factor. Assay II examines the ability of dentin bound biological response modifiers to stimulate directed cell movement and proliferation on dentin. We also propose to determine the specificity of various biological response modifiers on periodontal ligament cells, gingival fibroblasts, cells of osseous origin and gingival epithelial cells, In addition, we intend to examine the cell-cell interactions, both paracrine and autocrine, and their influences on periodontal regeneration. Finally we propose to study various biological response modifiers (determined to be effective from the in vitro studies) as potential promoters of healing at the dentin connective tissue interfaces in the presence of artifcial basement membranes as barriers to specific cell migration. The data generated will provide information and methodology on the feasibility that biochemically mediated tissue regeneration is possible by selective use of biological response modifiers.